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Biomedical subjects

D McDermott

Publications and source records attributed to D McDermott.

33 records · Page 2Linked to original sources

AICA-riboside: safety, tolerance, and pharmacokinetics of a novel adenosine-regulating agent.

AICA-riboside (5-amino-4-imidazole carboxamide ribonucleoside) is a novel adenosine-regulating agent that is currently being investigated for the treatment of ischemic heart disease. In a placebo-controlled, double-blind study in healthy men, we evaluated the safety and kinetics of the drug after oral and IV administration of 10, 25, 50, and 100 mg/kg doses. At each dose level, four subjects received active drug and two subjects received placebo with a 1-week wash-out period between the IV and oral doses. The drug was well tolerated at all dose levels with only mild and transient side effects reported in some instances by the subjects who received placebo and those patients who received the drug. The post-infusion plasma concentrations of AICA-riboside declined rapidly in a biphasic fashion, and the terminal elimination phase had a harmonic mean t1/2 beta of 1.4 hours. Total plasma clearance (CL), mean residence time (MRTIV), and volume of distribution at steady-state (VSS) were 2.5 L/hr/kg, 0.7 hr, and 1.6 L/kg, respectively. The drug was not protein bound, and there was rapid uptake and phosphorylation in RBCs to its 5'-monophosphate nucleotide. Renal clearance (CLR) was 0.2 L/hr/kg with only 8% of the IV dose excreted in the urine as intact AICA-riboside. Although there was a trend towards a decrease in CL with increasing dose, there were no significant differences (P greater than .05) in the mean estimates of t1/2 beta, CL, CLR, MRTIV and VSS associated with dose. The drug was poorly bioavailable (less than 5%) when administered orally in solution.

Administration, Oral↗

The effects of specialized training in alcohol information for counseling students.

The alcoholism problem in the United States has reached proportions impossible to ignore. It follows that we need trained professionals in significant numbers to deal with the alcoholic population. Graduate programs, however, provide little or no course offerings in the area of specific training for dealing with alcoholics. In academia some attempts have been made to address this situation. However, budget restrictions, limited marketability of counselors with specialized training, and the superiority of the generalist training model are some of the main arguments that have compromised adequate chemical dependence training. The research literature, however, is replete with studies indicating the need for specialized training to prepare mental health professionals to work as competent alcohol counselors. The focus of this research was to examine the effect of specific training for counseling students in preparing them to work with alcoholic clients. The results of the analyses indicated that a training session specifically designed for working with alcoholic populations significantly increased the objective knowledge base of counseling students, although the single training session was not enough to significantly improve subjective judgment and response scores. This research emphasizes a need for specialized training in counseling programs for alcohol counselors. Further, it is implied that training programs should include at least one semester-long course on alcohol remediation for counseling students.

Alcohol Drinking↗

COPBLAM III: infusional combination chemotherapy for diffuse large-cell lymphoma.

COPBLAM III, a polychemotherapy regimen consisting of cyclophosphamide, infusional vincristine, prednisone, infusional bleomycin, doxorubicin, and procarbazine, was administered to 51 patients with diffuse large-cell lymphoma. Ninety-six percent of patients age 60 or younger achieved a complete response (CR); none have relapsed. Overall, 88% of patients are alive and well and potentially in the survival plateau. For patients greater than 60 years, CR was obtained in 73%, with 42% potentially in the survival plateau, the difference resulting in part from four relapses, three toxic deaths, and one presumed unrelated death. These results in the elderly were paralleled by a relatively reduced ability to tolerate therapy. Toxicity was primarily pulmonary, occurring in 39% of patients, two of whom died. With an overall CR rate of 84%, of which 92% are sustained at a median follow-up of 40 months, COPBLAM III represents a highly effective treatment in a sizeable cohort of patients.

Adult↗

The COP-BLAM programs: evolving chemotherapy concepts in large cell lymphoma.

The cyclophosphamide, vincristine, prednisone, bleomycin, doxorubicin, procarbazine (COP-BLAM) programs of combination chemotherapy were administered to patients with advanced diffuse large cell lymphoma. The original COP-BLAM programs were designed to deliver intense multidrug therapy maximizing tumor kill. COP-BLAM programs IA and IB, easily administered on an outpatient basis, produced identical 73% complete remissions (CRs) and 55% long-term, disease-free survival (DFS). COP-BLAM III, an outgrowth of studies using infusional therapy, differed from COP-BLAM by using infusional bleomycin and vincristine alternated with bolus vincristine. With COP-BLAM III, 84% CRs, 76% "potential cures," and a 65% DFS were produced at a median follow-up time of 50 months. COD-BLAM IV, using four sequential cycles of infusional chemotherapy, high-dose alternating myelosuppressives (doxorubicin, cyclophosphamide), and cycle-active agents (methotrexate, cytarabine, and etoposide) produced 88% CRs, 67% potential cures, and a 64% DFS at a median follow-up of 24 months. COP-BLAM V employs four to six sequential cycles of infusional chemotherapy tailored to the rapidity of response. Preliminary results in patients with high-risk Hodgkin's disease suggest COP-BLAM V may be effective despite the shortened treatment time. In all programs, prognostic factors were critical determinants in the results achieved, particularly age and rapidity of response.

Antineoplastic Combined Chemotherapy Protocols↗

Professional burnout and its relation to job characteristics, satisfaction, and control.

Burnout scores for 104 professionals in the fields of college student personnel, health and mental health, administration and miscellaneous other professionals were correlated with ratings on 13 job characteristics, and ratings of satisfaction with, and control over, these characteristics. Results indicate significant positive correlations between the burnout scores and 10 of the 13 job characteristics. Significant positive correlations were found for burnout and all 13 items of job satisfaction. Significant negative correlations were found for 6 of the items where control was rated. Demographic variables of age, sex, marital status, employment status of spouse, dependents, number of hours worked, and being on call showed no significant correlations with burnout. Recommendations are made for continued research and theory building which take into account the concept of control over one's work environment.

Adult↗

Chymopapain-induced hypersensitivity following chemonucleolysis.

This study describes the changes in chymopapain-specific IgE antibody levels in patients following chemonucleolysis with Chymodiactin. Using the ChymoFAST method, chymopapain-specific IgE values were studied in 91 patients prior to and for 2 months post-Chymodiactin chemonucleolysis. A total of 8.8% (17/91) developed IgE levels greater than or equal to 0.06 IU/ml. Those patients with detectable IgE levels prior to chemonucleolysis were more likely than those with nondetectable preinjection levels (36.4% versus 4%) to develop chymopapain-specific IgE levels greater than or equal to 0.06 IU/ml.

Antibody Specificity↗

The relationship of parental drug use and parents' attitude concerning adolescent drug use to adolescent drug use.

The purpose of this study was to examine the relationship of two variables, parental drug use and parental attitude toward adolescent drug use, both as perceived by the adolescent respondent to his or her own use or nonuse of drugs. A sample of 106 drug-using and 96 nondrug-using adolescents was obtained through the use of the anthropological " snowball " technique. All respondents were administered a drug use history profile and a personal data questionnaire. In order to be classed as drug users, respondents had to have been using two or more recreational substances on a regular basis. Nondrug users were those who used no recreational drugs, although individuals who had tried alcohol or tobacco experimentally were included in this group. On the personal data form, respondents were asked to describe their parents' use of alcohol, tobacco, or other substances, and to indicate their parents' attitudes concerning adolescent use of drugs. Parental attitudes were classed as permissive if the respondent indicated that parents were indifferent about drug use, if they accepted a certain range of drugs, or if the decision were left up to the youth. A nonpermissive attitude was defined as one which would not accept drug use by the adolescent. Four 2 x 2 Chi-square analyses were used to determine significance of the relationship between adolescent drug use and parents' use or nonuse of drugs, parents' attitudes about adolescent use or nonuse and actual adolescent use or non-use, and this same attitudinal relationship looking at parent users and nonusers separately.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Inhibitors of phenylethanolamine N-methyltransferase and epinephrine biosynthesis. 3. Bis[tetrahydroisoquinoline]s.

7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline (SK&F 64139) is a potent inhibitor of phenylethanolamine N-methyltransferase (IC50 = 10 muM) that may have therapeutic utility in man. A series of related compounds in which two 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline molecules have been bridged from nitrogen to nitrogen by an unbranched alkyl chain have been prepared and have demonstrated potent inhibitory properties (0.08 to 2 muM). In contrast simple substitution on the nitrogen of 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline with a variety of substituents gives compounds with greatly diminished inhibitory potencies (IC50 = 2 to greater than 100 muM) relative to SK&F 64139. Kinetic studies with a C6 analogue have shown that it is competitive with respect to phenylethanolamine and uncompetitive with respect to S-adenosylmethionine. The increased potency of some of the bis analogues relative to that seen with the tetrahydroisoquinolines having larger alkyl groups on nitrogen suggests that several of the bis compounds show supplemented or cooperative binding to the enzyme, presumably as a result of the second tetrahydroisoquinoline moiety.

Animals↗

In vitro hypoxic cytotoxicity of nitroimidazoles: uptake and cell cycle phase specificity.

The hypoxic cytotoxicity of four different 2-nitroimidazoles of similar electron affinities but different lipophilicities was compared using EMT6/Ro mouse mammary tumor cells in exponential growth phase in severely (less than 20 ppm) hypoxic conditions. The relative cytotoxicities were misonidazole (MISO) = desmethylmisonidazole (9963) greater than SR-2508 much greater than SR-2555 indicating that the compounds with the lowest lipophilicity were less cytotoxic. The rates of uptake of these compounds were MISO greater than 9963 greater than SR-2508 = SR-2555. These data together with comparisons of the amounts of cell-associated compounds indicate that the similarity in toxicity of MISO and 9963 can be related to a general similarity in their pharmacokinetics, but that other unknown factors must be considered to explain the relative toxicity of SR-2508 and SR-2555. In other experiments, EMT6/Ro cells synchronized using centrifugal elutriation were most sensitive in hypoxia to MISO at the late G1--early S phase of the cell cycle. These data indicate the importance of considering cellular and subcellular distribution of these nitroimidazoles as well as possible cell cycle specificity for cytotoxicity in interpreting relative effectiveness of different compounds in responses of mixed populations of cells in cultures or tumors.

Animals↗